SCUBE3

Protein identityUniProt · HPA

UniProt accession

Q8IX30

Gene

SCUBE3

Ensembl

ENSG00000146197

Chromosome

6

Canonical length

993 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Subcellular location

Plasma membrane

Secretome location

Secreted to blood

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

993 residues, UniProt reviewed canonical sequence.

>Q8IX30|SCUBE3
     1  MGSGRVPGLC LLVLLVHARA AQYSKAAQDV DECVEGTDNC HIDAICQNTP RSYKCICKSG
    61  YTGDGKHCKD VDECEREDNA GCVHDCVNIP GNYRCTCYDG FHLAHDGHNC LDVDECAEGN
   121  GGCQQSCVNM MGSYECHCRE GFFLSDNQHT CIQRPEEGMN CMNKNHGCAH ICRETPKGGI
   181  ACECRPGFEL TKNQRDCKLT CNYGNGGCQH TCDDTEQGPR CGCHIKFVLH TDGKTCIETC
   241  AVNNGGCDSK CHDAATGVHC TCPVGFMLQP DRKTCKDIDE CRLNNGGCDH ICRNTVGSFE
   301  CSCKKGYKLL INERNCQDID ECSFDRTCDH ICVNTPGSFQ CLCHRGYLLY GITHCGDVDE
   361  CSINRGGCRF GCINTPGSYQ CTCPAGQGRL HWNGKDCTEP LKCQGSPGAS KAMLSCNRSG
   421  KKDTCALTCP SRARFLPESE NGFTVSCGTP SPRAAPARAG HNGNSTNSNH CHEAAVLSIK
   481  QRASFKIKDA KCRLHLRNKG KTEEAGRITG PGGAPCSECQ VTFIHLKCDS SRKGKGRRAR
   541  TPPGKEVTRL TLELEAEVRA EETTASCGLP CLRQRMERRL KGSLKMLRKS INQDRFLLRL
   601  AGLDYELAHK PGLVAGERAE PMESCRPGQH RAGTKCVSCP QGTYYHGQTE QCVPCPAGTF
   661  QEREGQLSCD LCPGSDAHGP LGATNVTTCA GQCPPGQHSV DGFKPCQPCP RGTYQPEAGR
   721  TLCFPCGGGL TTKHEGAISF QDCDTKVQCS PGHYYNTSIH RCIRCAMGSY QPDFRQNFCS
   781  RCPGNTSTDF DGSTSVAQCK NRQCGGELGE FTGYIESPNY PGNYPAGVEC IWNINPPPKR
   841  KILIVVPEIF LPSEDECGDV LVMRKNSSPS SITTYETCQT YERPIAFTAR SRKLWINFKT
   901  SEANSARGFQ IPYVTYDEDY EQLVEDIVRD GRLYASENHQ EILKDKKLIK AFFEVLAHPQ
   961  NYFKYTEKHK EMLPKSFIKL LRSKVSSFLR PYK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SCUBE3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

43 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SCUBE3.

Disease | AllUniProt

Conditions SCUBE3 is implicated in, by any mechanism.

• Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 (SSFSC2) MIM:619184

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 173 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2
• Abnormality of the dentition
• Abnormal facial shape
• Short stature
• Abnormality of the skeletal system

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.25

gnomAD pLI

1

gnomAD missense Z

2.7

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• positive regulation of BMP signaling pathway
• positive regulation of osteoblast differentiation
• signal transduction

Molecular functions

• BMP binding
• BMP receptor binding
• calcium ion binding
• identical protein binding

Cellular components

• cell surface
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• CUB domain
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• Tyrosine-protein kinase ephrin type A/B receptor-like
• EGF-like calcium-binding, conserved site
• NELL2-like, EGF domain
• Complement Clr-like EGF domain
• Spermadhesin, CUB domain superfamily
• NOTCH1, EGF-like calcium-binding domain
• Signal peptide, CUB and EGF-like domain-containing protein
• CUB domain
• Calcium-binding EGF domain
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Complement Clr-like EGF-like
• EGF domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Calcium
• Disulfide bond
• Dwarfism
• EGF-like domain
• Glycoprotein
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of SCUBE3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BMP2
• BMP4
• BMP7
• BMPR1A
• BMPR1B
• BMPR2